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Anti-nociceptive Activity of the Safflower (Carthamus tinctorius L.) in Mice | ||
Iranian Journal of Veterinary Medicine | ||
مقاله 18، دوره 19، شماره 4، دی 2025، صفحه 799-806 اصل مقاله (746.77 K) | ||
نوع مقاله: Original Articles | ||
شناسه دیجیتال (DOI): 10.32598/ijvm.19.4.1005581 | ||
نویسندگان | ||
Elaheh Tadayon1؛ Shahin Hassanpour* 2 | ||
1Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran. | ||
2Department of Basic Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran. | ||
چکیده | ||
Background: Pain is a traditional indication of an inflammatory reaction, manifesting allodynia and hyperalgesia. Carthamus tinctorius L. has demonstrated various biological activities. Objectives: This study aimed to determine the anti-nociceptive activity of the C. tinctorius L. in mice. Methods: A total of 105 adult male NMRI mice were randomly assigned to participate in five separate experiments, each consisting of four groups. In the initial trial, the mice were administered saline, an extract derived from C. tinctorius L. (100, 200 and 400 mg/kg) and morphine (5 mg/kg). In the second trial, the subjects were treated with saline, naloxone (2 mg/kg), extract of C. tinctorius L. (400 mg/kg), and a combination of extracts of C. tinctorius L. and naloxone. In trials 3-5, L-Name (10 mg/kg), cyproheptadine (4 mg/kg) and flumazenil (5 mg/kg) were administered instead of naloxone. Formalin was then injected, and paw-licking time (pain sense) was recorded. Results: According to the results, C. tinctorius L. exhibited a decrease in pain response compared to the control animals (P<0.05). Injection of naloxone in combination with C. tinctorius L. reduced the pain response during the formalin test (P<0.05). Injection of L-NAME combined with C. tinctorius L. led to increased pain response during the formalin test (P<0.05). Cyproheptadine was administered combined with C. tinctorius L. and pain response was reduced during the formalin test (P<0.05). Injection of flumazenil combined with C. tinctorius L. reduced pain response during the formalin test (P<0.05). Conclusion: These results suggested that the antinociceptive activity of C. tinctorius L. is mediated via the opioidergic, nitrergic, serotonergic and GABAergic systems in mice. | ||
کلیدواژهها | ||
Antinociceptive؛ Safflower؛ Nitrergic؛ Serotonergic؛ GABAergic | ||
اصل مقاله | ||
Introduction
In the second trial, the subjects were treated with saline, naloxone (2 mg/kg), an extract derived from the plant C. tinctorius L. (400 mg/kg), or a combination of an extract of C. tinctorius L. and naloxone (Figure 2).
In cases where two injections were administered, the subjects primarily received the antagonist, followed by C. tinctorius L. after 15 minutes. Additionally, 15 minutes later, formalin was injected, and the subsequent pain response was determined by assessing the time spent licking and biting the injected paw. In the third trial, the mice were intraperitoneally injected with saline, L-NAME (10 mg/kg), an extract of C. tinctorius L. (400 mg/kg) and a combination of an extract of C. tinctorius L. and L-NAME (Figure 3).
In the fourth trial, the mice were intraperitoneally injected with saline, cyproheptadine (4 mg/kg), an extract of C. tinctorius L. (400 mg/kg), and a combination of an extract of C. tinctorius L. and cyproheptadine (Figure 4).
In the fifth trial, the mice were intraperitoneally injected with saline, flumazenil (5 mg/kg), an extract of C. tinctorius L. (400 mg/kg) and a combination of an extract of C. tinctorius L. and flumazenil (Figure 5). The analgesic effect of C. tinctorius L. was assessed utilizing the formalin test, as described by Dubuisson and Dennis (1977), with certain modifications. The procedure involved injecting 20 µL formalin (0.5% formaldehyde in saline) into the plantar region of the right hind paw. Each animal was subsequently placed within a transparent plastic enclosure, and the time spent licking and/or biting the injected hind paw was recorded at 5-minute intervals over a 30-minute observation period. The formalin test comprises two distinct phases: an initial phase resulting from a direct impact on nociceptors, lasting for the first 5 minutes (neurogenic pain) and a later phase resulting from a direct impact of inflammatory mediators, lasting from 15 to 30 minutes (inflammatory pain) after formalin injection (Mota et al., 2011).
Results The results presented in Figure 5 demonstrate that the administration of flumazenil (5 mg/kg) did not elicit an antinociceptive response (P>0.05). Conversely, C. tinctorius L. (400 mg/kg) effectively inhibited the pain response in the injected paw compared to the control mice (P<0.05). Furthermore, the injection of flumazenil combined with C. tinctorius L. reduced the pain response during the formalin test (P<0.05). These results suggest that the GABAergic system mediates the observed effects of C. tinctorius L.
Kim et al. (2019) conducted a study that examined the inhibitory impact of C. tinctorius L. on nitric oxide (NO) production in HaCaT cells stimulated with lipopolysaccharides (LPS). The results indicated that the ethanol extract of C. tinctorius L. effectively hindered the LPS-stimulated NO production in HaCaT cells and reduced the messenger ribonucleic acid (mRNA) and protein expressions of inducible NO synthase (iNOS). HaCaT cells induced by LPS generate a swift inflammatory response that can release pro-inflammatory cytokines (IL-6 and IL-1) and inflammatory mediators (iNOS). Thus, the anti-nociceptive role of C. tinctorius L. is mediated via this mechanism. However, further research is needed to determine the accuracy of these findings. NO has a crucial nociceptive function in the central and peripheral nervous systems. Furthermore, it augments the generation or release of reactive oxygen species in cases of inflammatory pain (Ping et al., 2018). Naturally occurring compounds exhibit antioxidant and anti-inflammatory characteristics, effectively mitigating oxidative stress and neuropathic pain. By this, Dadpisheh et al. have shown that troxerutin enhances the levels of catalase, paraoxonase 1, glutathione peroxidase and NO in sciatic nerve ischemia-reperfusion injury cases. Oxidative stress, which results from an imbalance between the production of oxygen free radicals and the capacity for antioxidant action, impairs biological macromolecules and disrupts normal metabolism and physiology (Patil et al., 2024). Endogenous antioxidants exert their influence by scavenging oxygen free radicals, thereby delaying or inhibiting cellular damage, primarily through their ability to scavenge free radicals. Additionally, troxerutin effectively scavenges reactive oxygen species and reduces nuclear factor kappa B (NF-κB) expression in diabetic rats and patients afflicted by cardiovascular diseases (Najafi et al., 2018).
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